We propose to investigate metabolic and morphological aspects of various connective tissue macromolecules in connection with the development of vascular diseases in course of diabetes mellitus, using the following methods and techniques: 1) Measurements of the urinary excretion of glycosaminoglycans (polymeric and oligosaccharides); of collagen and elastin breakdown products (hydroxylysine glycosides and L-valyl-proline, respectively); 2) Measurements of levels of plasma glycosaminoglycans (both high and low sulfated species), and correlation with plasma lipo-proteins and blood glucose levels; 3) Measurements of high and low sulfated glycosaminoglycans in homogenates and media of cultured skin fibroblasts of diabetics and normal individuals; in extracts of normal and diabetic organs, such as aorta, myocardium and kidney, to be obtained immediately postmortem; correlation of these data with the amounts of collagen which may be extracted from cells or tissues with different and increasingly efficient solvents; 4) Electron microscopic studies (transmission and scanning) of large and medium size arterial specimens, and of renal glomerulo derived from diabetic and nondiabetic individuals, with the purpose of observing the structural features of the collagen, elastin and basement membrane structures at various stages of vascular involvement.